ABSTRACT
Intrahepatic cholestasis of pregnancy (ICP) represents the most common pregnancy-related liver disease in women. Women frequently present in the third trimester with pruritus and elevated serum bile acid and/or alanine transaminase levels. Clinical symptoms quickly resolve after delivery; however, recurrence in subsequent pregnancies has to be expected. Intrahepatic cholestasis of pregnancy is associated with increased perinatal complications, such as premature delivery, meconium staining of the amniotic fluid, respiratory distress, low Apgar scores, and even stillbirth. The risk for the fetus is significantly increased with maternal serum bile acid levels above 40âµmol/L, which characterize severe ICP. An important factor for ICP development is a rise of gestational hormones leading to cholestasis in genetically predisposed women. Variants in the bile salt export pump (BSEP) and the multidrug resistance protein 3 (MDR3) are most often identified in ICP. Here, we give an overview of the current literature on ICP and present the case of a woman with recurrent severe ICP. A common BSEP polymorphism as well as a rare MDR3 mutation may underlie the development of ICP in our patient. She had a premature delivery with meconium staining of the amniotic fluid. The neonate showed signs of respiratory distress with a low Apgar score. This case emphasizes that women with severe ICP have an increased risk for perinatal complications. Furthermore, severe ICP was associated with a MDR3 mutation, which has already been described in adult patients with liver cirrhosis. Thus, ICP may unmask an underlying MDR3 defect, which may predispose to development of hepatobiliary diseases such as gallstone disease, liver fibrosis/cirrhosis, as well as hepatobiliary malignancies. Therefore, genetic testing should be considered in women with severe as well as early onset ICP. Furthermore, regular follow-up should be discussed for women with genetic variants.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/genetics , ATP-Binding Cassette Transporters/genetics , Cholestasis, Intrahepatic/diagnosis , Cholestasis, Intrahepatic/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Pregnancy Complications/diagnosis , Pregnancy Complications/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 11 , Adult , Animals , Diagnosis, Differential , Female , Genetic Markers/genetics , Humans , Pregnancy , Prenatal Diagnosis/methodsABSTRACT
In the last decades, understanding of genetic variants contributing to liver disease development has considerably improved through novel genotyping techniques. Genetic variants of single genes are known to be decisive for the development of monogenetic liver diseases of varying severity. Identification of genetic variants is an important part of the diagnostic process, e.âg. the majority of patients with high iron [Fe] (HFE)-associated hemochromatosis carry the homozygous mutation p.C282Y. Detection of mutations in genes encoding hepatobiliary transport proteins like familial intrahepatic cholestasis 1 (FIC1), bile salt export pump (BSEP), or multidrug resistance protein 3 (MDR3) is the basis to differentiate various forms of intrahepatic cholestasis. Moreover, genetic variants in a variety of genes are known to act as disease modifiers and represent risk factors for disease progression and the development of cirrhosis or even hepatocellular carcinoma. Success of drug treatment or appearance of severe side effects can also be influenced by specific genetic variants. All these aspects underscore the increasing importance of genetic variants, which in the future may help to identify patients at risk for disease progression or help to guide treatment decisions. In the present overview, specific frequent genetic variants are summarized that play roles in monogenetic liver diseases, forms of intrahepatic cholestasis, gallstone development, fatty liver disease, drug-induced liver injury, and liver disease progression as well as hepatocellular carcinoma development.
Subject(s)
Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Liver Diseases/epidemiology , Liver Diseases/genetics , Polymorphism, Single Nucleotide/genetics , Genetic Variation/genetics , Humans , Incidence , Risk FactorsABSTRACT
HISTORY AND CLINICAL FINDINGS: A 45-year-old man had acute bouts of pain in the right lower thorax with radiation to the mid-thorax and upper abdomen. For 3 years he was known to have coronary heart disease, for 4 years arterial hypertension and for 8 months, as an accidentally discovered finding, a liver cyst 2.5 cm in diameter, as well as an inhomogeneous focal lesion, demonstrable only by sonography, lying dorsally and close to the diaphragm in the right lobe of the liver, 3.0 x 3.5 cm which was not detected by computed tomography or magnetic resonance imaging. Physical examination at admission detected epigastric pain on pressure but no other abnormalities. INVESTIGATIONS: Sonography showed the inhomogeneous hepatic lesion now to be 6.0 x 7.5 cm. Computed tomography demonstrated a space-occupying mass, 7.5 cm in diameter, dorsal to the hepatic cyst, partly hypo-, partly hyper-dense with marginal spotty enhancement after contrast-medium injection. TREATMENT AND COURSE: As acute bleeding into the focal hepatic lesion was suspected, a laparotomy was performed and liver segments VII and VIII resected. On inspection there was a sharply demarcated yellowish-white tumor with a central haemorrhagic softening. Histology revealed focal nodular hyperplasia (FNH) without signs of malignancy. CONCLUSION: In the case of a known but not definitively diagnosed focal hepatic lesion, acute upper abdominal pain can be a sign of acute bleeding into the lesion.
Subject(s)
Hemorrhage/etiology , Liver Diseases/complications , Liver/pathology , Acute Disease , Combined Modality Therapy , Diagnosis, Differential , Electrocardiography , Hemorrhage/diagnosis , Hemorrhage/therapy , Humans , Hyperplasia/complications , Hyperplasia/diagnosis , Hyperplasia/therapy , Liver/diagnostic imaging , Liver Diseases/diagnosis , Liver Diseases/therapy , Male , Middle Aged , Tomography, X-Ray ComputedABSTRACT
In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients.
Subject(s)
Autonomic Nervous System Diseases/physiopathology , Cholelithiasis/physiopathology , Diabetic Neuropathies/physiopathology , Gallbladder Emptying/physiology , Adult , Aged , Aged, 80 and over , Autonomic Nervous System/physiopathology , Autonomic Nervous System Diseases/diagnosis , Blood Pressure/physiology , Cholelithiasis/diagnosis , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/diagnosis , Female , Gallbladder/innervation , Heart Rate/physiology , Humans , Male , Middle Aged , Risk FactorsABSTRACT
In an in vitro study, 10 gallbladders of adult pigs and 6 gallbladders of lambs, all removed immediately after slaughtering, were stimulated in a water bath by electric means to induce active contraction. Gallbladder emptying was followed by ultrasonography employing five measurement procedures: (1) gallbladder width, (2) longitudinal planimetry, (3) transverse planimetry, (4) ellipsoid method, and (5) sum of cylinders method. In an in vivo investigation, gallbladder emptying of 30 volunteers (12 healthy subjects, 18 diabetics) was evaluated in the same way after ingestion of a fatty meal. Gallbladder width was found to be unsuitable to estimate the decrease in gallbladder volume due to a nonlinear relation of the parameters. Longitudinal planimetry tended to be less valid than transverse planimetry in assessing gallbladder volume reduction. The most valid estimation of gallbladder volume decreases was obtained by the two three-dimensional procedures. However, in neither in vitro nor in vivo could a significant difference between the sum of cylinders method and the ellipsoid method in determining relative volume reduction be established. We conclude that a three-dimensional measurement procedure should be used for valid assessments of gallbladder motility. However, according to our data there is no advantage in using the time-consuming sum of cylinders method compared to the simple ellipsoid method.